Evidence map›Paper›PMID 25052763›Full record

ArticleMucosal immunology2015

Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides universal protection against diverse subtypes.

X Fan, A M Hashem, Z Chen, C Li, T Doyle, Y Zhang, Y Yi, A Farnsworth, K Xu, Z Li and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Mucosal immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. CD40 Ligand Potentiates Immunogenecity ofCurrent issues in molecular biology · 2025
    Article
  3. Article
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  15. Vaccines · 2021
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  18. Review
  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

X Fan1] National Institutes for Food and Drug Control, Beijing, China [2] Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
A M Hashem1] Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada [2] Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia [3] Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia [4] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Z ChenShanghai Institute of Biological Products, Shanghai, China.
C LiNational Institutes for Food and Drug Control, Beijing, China.
T Doyle1] Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Y ZhangDepartment of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Y YiShanghai Institute of Biological Products, Shanghai, China.
A FarnsworthCentre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
K XuNational Institutes for Food and Drug Control, Beijing, China.
Z LiNational Institutes for Food and Drug Control, Beijing, China.
R HeNational Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
X Li1] Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
J WangNational Institutes for Food and Drug Control, Beijing, China.
National Institutes for Food and Drug Control · CNHealth Canada · CAAir Force Medical University · CNPublic Health Agency of Canada · CAUniversity of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The influenza viral hemagglutinin (HA) is comprised of two subunits. Current influenza vaccine predominantly induces neutralizing antibodies (Abs) against the HA1 subunit, which is constantly evolving in unpredictable fashion. The other subunit, HA2, however, is highly conserved but largely shielded by the HA head domain. Thus, enhancing immune response against HA2 could potentially elicit broadly inhibitory Abs. We generated a recombinant adenovirus (rAd) encoding secreted fusion protein, consisting of codon-optimized HA2 subunit of influenza A/California/7/2009(H1N1) virus fused to a trimerized form of murine CD40L, and determined its ability of inducing protective immunity upon intranasal administration. We found that mice immunized with this recombinant viral vaccine were completely protected against lethal challenge with divergent influenza A virus subtypes including H1N1, H3N2, and H9N2. Codon-optimization of HA2 as well as the use of CD40L as a targeting ligand/molecular adjuvant were indispensable to enhance HA2-specific mucosal IgA and serum IgG levels. Moreover, induction of HA2-specific T-cell responses was dependent on CD40L, as rAd secreting HA2 subunit without CD40L failed to induce any significant levels of T-cell cytokines. Finally, sera obtained from immunized mice were capable of inhibiting 13 subtypes of influenza A viruses in vitro. These results provide proof of concept for a prototype HA2-based universal influenza vaccine.

Indexed as

AdenoviridaeAnimalsAntibodies, NeutralizingAntigenic VariationCD40 LigandDogsFemaleHEK293 CellsHeLa CellsHemagglutinin Glycoproteins, Influenza VirusHumansImmunizationInfluenza A virusInfluenza, HumanInfluenza VaccinesMadin Darby Canine Kidney CellsAntibodies, NeutralizingCD40 LigandH1N1 virus hemagglutininHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesProtein SubunitsRecombinant Fusion Proteins

Identifiers

PMID25052763
PMCPMC4269809
OpenAlexW2031342500

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.